Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Isolation and Characterization of Porcine Sapelovirus from the PDCoV-Positive Sample and Its Molecular Epidemiology in Henan Province, China

Porcine sapelovirus (PSV) is an emerging swine enteric virus that can cause various disorders including acute diarrhea, respiratory distress, reproductive failure, and polioencephalomyelitis in pigs. In this study, we isolated a PSV strain HNHB-01 from a clinical porcine deltacoronavirus- (PDCoV-) positive intestinal content of a diarrheic piglet. PSV was first identified using the small RNA deep sequencing and assembly, and further identified by the electron microscopic observation and the immunofluorescence assay. Subsequently, this virus was serially passaged in swine testis (ST) cells, and the complete genomics of PSV HNHB-01 passage 5 (P5), P30, P60, and P100 were sequenced and analyzed. 9 nucleotide mutations and 7 amino acid changes occurred in the PSV HNHB-01 P100 strain when compared with the PSV HNHB-01 P5. Pathogenicity investigation showed that orally inoculation of PSV HNHB-01 P30 could cause obvious clinical symptoms and had broad tissue tropism in 5-day-old piglets. Epidemiological investigation revealed that PSV infections and the coinfections of diarrhea coronaviruses were highly prevalent in swine herds. The complete genomes of 8 representative PSV epidemic strains were sequenced and analyzed. Phylogenetic analysis revealed that the PSV epidemic strains were closely related to other PSV reference strains that located in the Chinese clade. Furthermore, recombination analysis revealed that the recombination events were occurred in downstream of the 2C region in our sequenced PSV HNNY-02/CHN/2018 strain. Our results provided theoretical basis for future research studies of the pathogenic mechanism, evolutionary characteristics, and the development of vaccines against PSV.

SARS-CoV-2 VARIANTS-DEPENDENT INFLAMMASOME ACTIVATION

Background: Innate immunity is the first line of defense in response to pathogens, which acts locally and also leads the stimulation of adaptive immunity through at least with IL-1beta secretion. It has been shown that SARSCoV- 2 infection triggered the NLRP-3 inflammasome activation and the IL-1beta secretion. The aim of this study was to analyze and compare the level of IL-1beta secretion that is one of the most important innate immunity cytokines, in monocyte-like cells infected with 6 different variants of the SARS-CoV-2. Method(s): Six SARS-CoV-2 variants (historical (B.1, D614G), Alpha, Beta, Gamma, Delta and Omicron BA.1) were isolated from COVID-19 hospitalized patients. Viral stocks were obtained by inoculation in Vero and Vero-TRMPSS2 cells. THP-1 monocyte-like cells were cultured with RPMI-hepes 10% FBS-0.05 mM 2-mercaptoethanol. A total of 5 x 104 of THP-1 cells was plated per well in 96-wells plate and differentiated with 10nM of PMA for 24h. Differenciated- THP-1 were first primed with LPS 1mug/ml for 2h and infected with different SARS-CoV-2 variants with a MOI 0.1. IL-1beta was measured by luminescence in the supernatant after 24 h of infection. Result(s): We analyzed and compared IL-1beta secretion between SARS-CoV-2 virus 6 sublineages after infection of monocytes like THP-1. We observed that THP-1 cells infected with SARS-CoV-2 variants presented a significantly higher IL-1beta secretion than non-infected cells. Moreover, some SARS-CoV-2 variants led to a stronger IL-1beta secretion, and particularly we observed a significantly higher level of IL-1beta cells infected with Omicron BA.1 sublineage compared to other variants. Indeed, Omicron BA.1 infected cells presented the higher IL-1beta secretion (median 385.7 pg/ml IQR[302.6-426.3]) follows by the Delta variants and the historical variants (median 303.6 [266.3-391.9] and 281.9 [207.2-410], respectively). Alpha, Beta and Gamma variants presented the lowest IL-1beta secretion (median 228.1 [192.5-276.4], 219.1 [185.1-354.2] and 211 [149.8- 228.8]). Conclusion(s): We observed the inflammasome activation for the 6 SARS-CoV-2 sublineages with a variation in level of IL-1beta secretion. Indeed, our results suggested that Omicron BA.1 was more recognized by the innate immune cells than other SARS-CoV-2, which could in part, with its upper respiratory tract tropism, possibly explain its less clinical virulence. Taking together, these results suggest that the innate immunity response and precisely, IL-1beta secretion pathways were activated in a SARS-CoV-2 variants-dependent manner.

cGAS-STING PATHWAY LIMITS SARS-CoV-2 REPLICATION IN ACE2+ AIRWAY CELL LINES

Background: We previously screened 10 human lung and upper airway cell lines expressing variable levels of endogenous ACE2/TMPRSS2. We found that H522 human lung adenocarcinoma cells supported SARS-CoV-2 replication independent of ACE2, whereas the ACE2 positive cell lines were not permissive to infection. Type I/III interferons (IFNs) potently restrict SARS-CoV-2 replication through the actions of hundreds of interferon-stimulated genes (ISGs) that are upregulated upon IFN signaling. Here we report that a number of ACE2 positive airway cell lines are unable to support SARS-CoV-2 replication due to basal activation of the cGAS-STING DNA sensing pathway and subsequent upregulation of IFNs and ISGs which restrict SARS-CoV-2 replication. Method(s): SARS-CoV-2 WT strain 2019-nCoV/USA-WA1/2020 viral replication was detected through analysis of cell associated RNA. RNA sequencing was used to study the basal level of genes in the type-I IFN pathway in the 10 cell lines, which was further validated by western blotting and qRT-PCR. A panel of 5 cell lines, with varying expression levels of ACE2 and TMPRSS2, were pre-treated with Ruxolitinib, a JAK1/2 inhibitor. A siRNA-mediated screen was used to determine the molecular basis of basally high expression of ISGs in cell lines. CRISPR knockout of IFN-alpha receptor and cGAS-STING pathway components was conducted in parallel Results: Here we show that higher basal levels of IFN pathway activity underlie the inability of ACE2+ cell lines to support virus replication. Importantly, this IFN-induced block can be overcome by chemical inhibition and genetic disruption of the IFN signaling pathway or by ACE2 overexpression, suggesting that one or more saturable ISGs underlie the lack of permissivity of these cells. Ruxolitinib treatment increased SARS-CoV-2 RNA levels by nearly 3 logs in OE21 and SCC25. Furthermore, the baseline activation of the STING-cGAS pathway accounts for the high ISG levels and genetic disruption of the cGAS-STING pathway enhances levels by nearly 2 and 3 logs of virus replication in the two separate ACE2+ cell line models respectively. Conclusion(s): Our findings demonstrate that cGAS-STING-dependent activation of IFN-mediated innate immunity underlies the inability of ACE2+ airway cell lines to support SARS-CoV-2 replication. Our study highlights that in addition to ACE2, basal activation of cGAS-STING pathway, IFNs and ISGs may play a key role in defining SARS-CoV-2 cellular tropism and may explain the complex SARS-CoV- 2 pathogenesis in vivo.

Fc RECEPTOR-MEDIATED INFECTION OF MYELOID CELLS BY SARS-CoV-2

Background: The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection remains unclear. Method(s): Using anti-SARS-CoV-2 mAbs with a range of neutralisation potencies and binding specificities, we performed a detailed assessment of mAb-mediated infection of monocytes/macrophages. THP-1 cells were used as a model system, with results confirmed in primary macrophages. Result(s): Infection of THP-1 cells was seen via mAbs targeting the spike RBD, but not with those targeting the NTD or S2 subunit. mAbs with the most consistent potential to mediate infection targeted a conserved region of the RBD (group 1/class IV). No infection was seen with the same quantity of virus but in the absence of antibody, and pre-treating the cells with FcgammaRI and -II blocking antibodies inhibited infection. Thus, antibody-FcR interactions are able to expand the tropism of SARS-CoV-2. Time-course studies demonstrated high-level and productive infection. Studies performed in human iPSC-derived macrophages and primary monocyte-derived macrophages paralleled results seen in THP-1 cells but with lower infection levels. Up to 2% of macrophages were infected, with infected cells appearing multinucleated and syncytial. Addition of ruxolitinib, an inhibitor of JAK1/2 signalling, increased infection up to 10-fold, indicating limitation of infection through innate immune mechanisms. Sera from primary infections (n=80) mediated rare infection events, with a minority of samples (n=3) promoting significant infection. Competition assays confirmed results seen in sera, with the addition of neutralising mAbs diminishing the infection seen with infection-mediating mAbs. Thus, the presence of antibodies with potential to mediate infection is not sufficient to predict myeloid cell infection, rather, the context in which the antibodies are produced is key. Conclusion(s): We hypothesise that a nascent antibody response during peak viral replication in primary infection presents a window of opportunity for myeloid cells to become infected, while establishment of a robust polyclonal response via vaccination or prior infection reduces the likelihood of this occurring. Infection via antibody-FcR interactions could contribute to pathogenesis in primary infection, systemic virus spread or persistent infection.

Cellular tropism of SARS-CoV-2 in various organs - A Histopathology and Immunohistochemistry study on Covid-19 Deaths

Background and objectives: SARS-C0V-2 infections have varied manifestations among individuals ranging from asymptomatic or mild symptoms to severe disease and death. This study is done to look into various histopathological changes in lung, liver, and kidney tissues among Covid19 positive autopsies with cellular tropism and viral load among various organs by immunohistochemistry (IHC) for the SARS-C0V-2 viral marker. Method(s): A prospective descriptive study of core biopsies from covid19 positive autopsies from the lung, liver, and kidneys were taken from 20 cases. A routine histopathological examination of the tissues with IHC staining for SARS-CoV-2 cocktail antibodies was performed and assessed. Result(s): Histopathological changes in the lung, liver, and kidney tissues showed changes of varying severity. On IHC, in the lung, the tropism for SARS-CoV-2 was seen in pneumocytes, bronchial epithelial cells, endothelial cells, and macrophages. In the kidney, tropism was seen towards tubular epithelial cells and endothelial cells. In the liver, hepatocytes and bile duct epithelial cells were positive. Variable viral density was seen in different organs which varied from case to case. The density of the viral load was highest in the lung and lower in the kidney and least in the liver. Conclusion(s): In this study the various histopathological changes and cellular tropism of the SARS-CoV-2 among Lung, liver, and kidney tissues have been described and compared with various similar studies across the globe.Copyright © 2023 International Journal of Life Sciences Biotechnology and Pharma Research. All rights reserved.

Manifestaciones extrapulmonares de COVID-19.

Coronaviruses are a large family of single-stranded ARN viruses that infect a wide variety of animals, including humans. The SARS-CoV-2 virus, which is responsible for the disease called COVID-19, has infected 27,249,308 people and caused 890,971 deaths worldwide until September 7, 2020. Considering the genetic similarities between SARS-CoV-2 and the epidemic coronaviruses SARS-CoV and MERS, presumably they share tropisms for specific cell lines and systemic conditions. The clinical and paraclinical characteristics of this new virus have been described in detail at the pulmonary level, although there is increasing evidence that it is a multisystemic agent. In the present work, we describe the extrapulmonary manifestations of COVID-19 reported to date, including hematological, cardiovascular, neurological, renal, muscular, ophthalmological, endocrine-metabolic, gastrointestinal, hepatobiliary, cutaneous and in special populations: pediatric (including multisystemic inflammatory syndrome) and pregnant women. It is essential to know the systemic complications of SARS-CoV-2 infection when managing these patients, given the potential risk to life of the most serious manifestations. Therefore, it is advisable to consider them in a targeted manner and provide timely treatment as far as possible.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Cardiovascular risk among patients recovered from COVID-19 in the short and medium term: what does the current evidence conclude?.

Cardiovascular risk and diseases among patients recovered from COVID-19 is a recent field of study in the world medical literature and is also of vital importance because a large number of patients develop complications once the acute phase of the disease is over. The broad spectrum of myocardial injury in cardiovascular diseases can range from the asymptomatic elevation of cardiac troponin levels to the development of fulminant myocarditis and/or circulatory shock, which can leave significant sequelae. Despite the fact that there is no clear strategy to treat cardiac events that occur during COVID-19 infection and taking into account that treatment is mainly aimed at relieving patients' symptoms as they arise, the objective of this work was to find out and collect current evidence on this subject, so that readers can be offered a reference guide in Spanish that contributes to the development of their health profession. The methodology used was a literature search in databases including Medline, Scopus and ScienceDirect within a time window between 2019 and 2022. The main results revealed that the molecular and pathophysiological mechanisms involved in post-COVID-19 syndrome include the renin-angiotensin-aldosterone system since SARS-CoV-2 tropism is linked to angiotensin-converting enzyme 2. This causes an alteration of the neurohumoral response of the cardiovascular, renal and digestive systems, generating deficits in the signaling pathways and causing direct damage to the heart, lungs and other organs. Post-COVID-19 syndrome, in general, is defined as the occurrence or persistence of symptoms three or four weeks after the acute phase of the disease. This could then be considered as a time window of risk and strict follow-up to assess in a personalized way the risk among the different groups of patients, especially those with a past history of cardiovascular disease. The main results revealed disorders such as heart failure, arrhythmias, pericarditis and myocarditis, which require early detection and occur days or even weeks after the acute phase of COVID-19.Copyright © La revista. Publicado por la Universidad de San Martin de Porres, Peru.

Multi-facetic tropism of SARS-CoV-2.

SARS-CoV-2 has a predilection for cell groups that are rich in ACE2 and TMPRSS2 receptors, which are distributed throughout the human body, which means that, in addition to the primary site of contagion or primary infection, which is the respiratory system, the virus tends to spread by different mechanisms, affecting practically all the known organs, apparatuses and systems, with which its tropism becomes extensive, being able to condition diverse pictures together with the respiratory one.Copyright © 2023 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Cell-Specific Mechanisms in the Heart of COVID-19 Patients.

From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type-specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type-specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.

Novel recombinant avian infectious bronchitis viruses from chickens in Korea, 2019-2021.

Infectious bronchitis virus (IBV) has evolved through various mutation mechanisms, including antigenic drift and recombination. Four genotypic lineages of IBVs including GI-15, GI-16, GI-19, and GVI-1 have been reported in Korea. In this study, we isolated two IBVs from chicken farms, designated IBV/Korea/289/2019 (K289/19) and IBV/Korea/163/2021 (K163/21), which are two distinct natural recombinant viruses most likely produced by genetic reassortment between the S1 gene of K40/09 strain (GI-19 lineage) and IBV/Korea/48/2020 (GI-15 lineage) in co-infected commercial chickens. Comparative sequence analysis of hypervariable regions (HVRs) revealed that the K289/19 virus had similar HVR I and II with the K40/09 virus (100% and 99.2% nucleotide sequence identity, respectively), and HVR III with the IBV/Korea/48/2020 virus (100% nucleotide sequence identity). In contrast, the K163/21 virus had HVR I and II similar to the IBV/Korea/48/2020 virus (99.1% and 99.3% nucleotide sequence identity, respectively), and HVR III to the K40/09 virus (96.6% nucleotide sequence identity). The K289/19 virus exhibited similar histopathologic lesions, tissue tropism in trachea and kidney, and antigenicity with the parental K40/09 virus. The K163/21 exhibited similar pathogenicity and tissue tropism with the K40/09 virus, which were similar results with the isolate K289/19. However, it showed a lower antigenic relatedness with both parental strains, exhibiting R-value of 25 and 42, respectively. The continued emergence of the novel reassortant IBVs suggests that multiple recombination events have occurred between different genotypes within Korea. These results suggest that antigenic profiles could be altered through natural recombination in the field, complicating the antigenic match of vaccine strains to field strains. Enhanced surveillance and research into the characteristics of newly emerging IBVs should be carried out to establish effective countermeasures.

An Overview of Adenovirus Vector-based Vaccines against SARS-CoV-2

Adenovirus vectors have been employed to develop a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for curtailing the Covid-19 pandemic spreading. Many different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as an antigen. Spike (S) protein is comprised of S1 and S2 subunits, in which the receptor-binding domain (RBD) of S1 is responsible for recognizing and engaging with its host cellular receptor protein angiotensin-converting enzyme 2 (ACE2), S2 accounts for membrane fusion of virus and host cell. Chimpanzee adenovirus was also used as a vector vaccine for SARS-CoV-2 (ChAdSARS-CoV-2-S) by intramuscular injection, and intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced, with several vaccines receiving Emergency Use Authorization (EUA). It was shown that rhesus macaques were protected from SARS-CoV-2 challenge after a month of being vaccinated with ChAd-SARS-CoV-2-S. A single intranasal or two intramuscular ChAd-SARSCoV-2-S vaccines could induce humoral antibodies and T cell responses to protect the upper and lower respiratory tract against SARS-CoV-2. As the effectiveness was demonstrated in non-human primates, ChAd-SARS-CoV-2-Sa potential option for preventing SARS-CoV-2 infection in humans. However, detecting novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs monitoring. Moreover, the cause of recently documented rare cases of vaccine indicated immune thrombotic thrombocytopenia. This review article provided details for the adenovirus vector vaccine for SARS-CoV-2 in humans and tried to provide solutions to the adenovirus vector hemagglutinin issueCopyright © 2023, World's Veterinary Journal.All Rights Reserved.

Natural selection differences detected in key protein domains between non-pathogenic and pathogenic feline coronavirus phenotypes.

Feline coronaviruses (FCoVs) commonly cause mild enteric infections in felines worldwide (termed feline enteric coronavirus [FECV]), with around 12 per cent developing into deadly feline infectious peritonitis (FIP; feline infectious peritonitis virus [FIPV]). Genomic differences between FECV and FIPV have been reported, yet the putative genotypic basis of the highly pathogenic phenotype remains unclear. Here, we used state-of-the-art molecular evolutionary genetic statistical techniques to identify and compare differences in natural selection pressure between FECV and FIPV sequences, as well as to identify FIPV- and FECV-specific signals of positive selection. We analyzed full-length FCoV protein coding genes thought to contain mutations associated with FIPV (Spike, ORF3abc, and ORF7ab). We identified two sites exhibiting differences in natural selection pressure between FECV and FIPV: one within the S1/S2 furin cleavage site (FCS) and the other within the fusion domain of Spike. We also found fifteen sites subject to positive selection associated with FIPV within Spike, eleven of which have not previously been suggested as possibly relevant to FIP development. These sites fall within Spike protein subdomains that participate in host cell receptor interaction, immune evasion, tropism shifts, host cellular entry, and viral escape. There were fourteen sites (twelve novel sites) within Spike under positive selection associated with the FECV phenotype, almost exclusively within the S1/S2 FCS and adjacent to C domain, along with a signal of relaxed selection in FIPV relative to FECV, suggesting that furin cleavage functionality may not be needed for FIPV. Positive selection inferred in ORF7b was associated with the FECV phenotype and included twenty-four positively selected sites, while ORF7b had signals of relaxed selection in FIPV. We found evidence of positive selection in ORF3c in FCoV-wide analyses, but no specific association with the FIPV or FECV phenotype. We hypothesize that some combination of mutations in FECV may contribute to FIP development, and that it is unlikely to be one singular 'switch' mutational event. This work expands our understanding of the complexities of FIP development and provides insights into how evolutionary forces may alter pathogenesis in coronavirus genomes.

Molecular Characterization of 4/91 Infectious Bronchitis Virus Leading to Studies of Pathogenesis and Host Responses in Laying Hens.

Infectious bronchitis virus (IBV) initially establishes the infection in the respiratory tract and then spreads to other tissues depending on its virulence. During 2011-2018, the 4/91 IBV strain was isolated from poultry flocks affected by decreased egg production and quality in Eastern Canada. One of the Canadian 4/91 IBV isolates, IBV/Ck/Can/17-038913, was propagated in embryonated chicken eggs and molecularly characterized using whole genome sequencing. An in vivo study in laying hens was conducted to observe if IBV/Ck/Can/17-038913 isolate affects the egg production and quality. Hens were infected with IBV/Ck/Can/17-038913 isolate during the peak of egg lay, using a standard dose and routes maintaining uninfected controls. Oropharyngeal and cloacal swabs were collected at predetermined time points for the quantification of IBV genome loads. At 6 and 10 days post-infection, hens were euthanized to observe the lesions in various organs and collect blood and tissue samples for the quantification of antibody response and IBV genome loads, respectively. Egg production was not impacted during the first 10 days following infection. No gross lesions were observed in the tissues of the infected birds. The IBV genome was quantified in swabs, trachea, lung, proventriculus, cecal tonsils, kidney, and reproductive tissues. The serum antibody response against IBV was quantified in infected hens. In addition, histological changes, and recruitment of immune cells, such as macrophages and T cell subsets in kidney tissues, were measured. Overall, data show that IBV/Ck/Can/17-038913 isolate is not associated with egg production issues in laying hens infected at the peak of lay, while it demonstrates various tissue tropism, including kidney, where histopathological lesions and immune cell recruitments were evident.

ACE2 partially dictates the host range and tropism of SARS-CoV-2.

COVID-19, which is caused by SARS-CoV-2, has been declared a global pandemic. Although effective strategies have been applied to treat the disease, much is still unknown about this novel virus. SARS-CoV-2 enters host cells through ACE2, which is a component of the angiotensin-regulating system. Binding of the SARS-CoV-2 S protein to ACE2 is a prerequisite for SARS-CoV-2 infection. Many studies have indicated a close relationship between ACE2 expression and SARS-CoV-2 infection. The structural basis of receptor recognition by SARS-CoV-2 has been analyzed in detail. The diversification of the ACE2 sequence due to ACE2 polymorphisms and alternative splicing has to a large extent affected the susceptibility of different species. Differential ACE2 expression makes specific populations more prone to be infected, and ACE2 also plays a role in the broad tropism of SARS-CoV-2 in human organs and tissues. In this review, we comprehensively summarize how the ACE2 expression profile affects the host range and tropism of SARS-CoV-2, which will provide mechanistic insights into the susceptibilities and outcomes of SARS-CoV-2 infection.

Impact and Inescapable Effects of Coronavirus: History to Modern Pandemic Episode

Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection causing a pandemic that emerged in 2019 initially in China involving 13.8% cases with severe, and 6.1% with critical course and later throughout the globe. Vaccines or antiviral medications are yet to be used to prevent or treat infections of Human Coronavirus (HCoV). The much-discovered HCoV found in 2003, SARS-COVID-19, which caused respiratory syndrome, has special pathogenesis as it causes respiratory tract infection. The coronavirus spike protein's association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. SARS, COVID-19, infects human cells by binding to angiotensin-converting enzyme 2 (ACE2) receptor and uses the TMPRSS2 cell protease to activate it. Lungs are most affected by COVID-19 as host cells are accessed by the virus through ACE2, which is most abundant in alveolar cells of the lungs. Special attention and efforts should be given in reducing transmission in vulnerable populations, including infants, health care providers and the elderly. COVID 19, is the main causative agent of potentially lethal disease and is of significant concern for global public health and in pandemics which was highlighted in this review.Copyright © 2021 Bentham Science Publishers.

Lentiviral Vectors as a Vaccine Platform against Infectious Diseases.

Lentiviral vectors are among the most effective viral vectors for vaccination. In clear contrast to the reference adenoviral vectors, lentiviral vectors have a high potential for transducing dendritic cells in vivo. Within these cells, which are the most efficient at activating naive T cells, lentiviral vectors induce endogenous expression of transgenic antigens that directly access antigen presentation pathways without the need for external antigen capture or cross-presentation. Lentiviral vectors induce strong, robust, and long-lasting humoral, CD8+ T-cell immunity and effective protection against several infectious diseases. There is no pre-existing immunity to lentiviral vectors in the human population and the very low pro-inflammatory properties of these vectors pave the way for their use in mucosal vaccination. In this review, we have mainly summarized the immunological aspects of lentiviral vectors, their recent optimization to induce CD4+ T cells, and our recent data on lentiviral vector-based vaccination in preclinical models, including prophylaxis against flaviviruses, SARS-CoV-2, and Mycobacterium tuberculosis.

Intestinal Tropism of a Betacoronavirus (Merbecovirus) in Nathusius's Pipistrelle Bat (Pipistrellus nathusii), Its Natural Host.

The emergence of several bat coronavirus-related disease outbreaks in human and domestic animals has fueled surveillance of coronaviruses in bats worldwide. However, little is known about how these viruses interact with their natural hosts. We demonstrate a Betacoronavirus (subgenus Merbecovirus), PN-ßCoV, in the intestine of its natural host, Nathusius's Pipistrelle Bat (Pipistrellus nathusii), by combining molecular and microscopy techniques. Eighty-eight P. nathusii bat carcasses were tested for PN-ßCoV RNA by RT-qPCR, of which 25 bats (28%) tested positive. PN-ßCoV RNA was more often detected in samples of the intestinal tract than in other sample types. In addition, viral RNA loads were higher in intestinal samples compared to other sample types, both on average and in each individual bat. In one bat, we demonstrated Merbecovirus antigen and PN-ßCoV RNA expression in intestinal epithelium and the underlying connective tissue using immunohistochemistry and in situ hybridization, respectively. These results indicate that PN-ßCoV has a tropism for the intestinal epithelium of its natural host, Nathusius's Pipistrelle Bat, and imply that the fecal-oral route is a possible route of transmission. IMPORTANCE Virtually all mammal species circulate coronaviruses. Most of these viruses will infect one host species; however, coronaviruses are known to include species that can infect multiple hosts, for example the well-known virus that caused a pandemic, SARS-CoV-2. Chiroptera (bats) include over 1,400 different species, which are expected to harbor a great variety of coronaviruses. However, we know very little about how any of these coronaviruses interact with their bat hosts; for example, we do not know their modes of transmissions, or which cells they infect. Thus, we have a limited understanding of coronavirus infections in this important host group. The significance of our study is that we learned that a bat coronavirus that occurs in a common bat species in Europe has a tropism for the intestines. This implies the fecal-oral route is a likely transmission route.

Examining the associations between COVID-19 infection and pediatric type 1 diabetes.

INTRODUCTION: The COVID-19 pandemic represents an unprecedented challenge for public health worldwide, not only for the very high number of cases and deaths but also due to a wide variety of indirect consequences. Among these, the possible relationship between SARS-CoV-2 infection and type 1 diabetes (T1D) in pediatric age has aroused notable interest in the scientific community. AREAS COVERED: This perspective article aims to focus on the epidemiological trend of T1D during the pandemic, the diabetogenic role of SARS-CoV-2, and the influence of preexisting T1D on COVID-19 outcomes. EXPERT OPINION: The incidence of T1D has considerably changed during the COVID-19 pandemic, but any direct role of SARS-CoV-2 is uncertain. It is more likely that SARS-CoV-2 infection acts as an accelerator of pancreatic ß-cell immunological destruction, which is activated by known viral triggers whose spread has been abnormal during these pandemic years. Another interesting aspect to consider is the role of immunization as a potential protective factor both for T1D development and the risk of severe outcomes in already diagnosed patients. Future studies are still required to address unmet needs, including the early use of antiviral drugs to reduce the risk of metabolic decompensation in children with T1D.

New Postmortem Perspective on Emerging SARS-CoV-2 Variants of Concern, Germany.

We performed autopsies on persons in Germany who died from COVID-19 and observed higher nasopharyngeal SARS-CoV-2 viral loads for variants of concern (VOC) compared with non-VOC lineages. Pulmonary inflammation and damage appeared higher in non-VOC than VOC lineages until adjusted for vaccination status, suggesting COVID-19 vaccination may mitigate pulmonary damage.